Neurodevelopmental Needs in Young Boys with Duchenne Muscular Dystrophy (DMD): Observations from the Cooperative International Neuromuscular Research Group (CINRG) DMD Natural History Study (DNHS).
We describe the neurodevelopmental needs in this young cohort at study enrollment as reported by the parent or primary care-giver. We present data that supports that young boys with DMD have a high prevalence of neurodevelopmental needs as reported by parent or care-giver. Further, boys with DMD mutations between exons 45-50 reported higher cognitive problems. There was no relationship between neurodevelopmental needs and glucocorticoid use. We conclude that there is an unmet, critical medical need in DMD to develop pragmatic solutions for early detection and intervention of neurodevelopmental needs during a window of neu...
Source: PLOS Currents Muscular Dystrophy - October 17, 2018 Category: Neurology Authors: Mathula Thangarajh Source Type: research

Exploratory Profiling of Urine MicroRNAs in the dy2J/dy2J Mouse Model of LAMA2-CMD: Relation to Disease Progression
In this study we aimed at profiling miRNA expression in urine from dy2J/dy2J mice to assess their potential for monitoring disease progression. Three distinct time points (three, four and six weeks of age) were chosen to represent asymptomatic, initial symptoms and established disease, respectively. Here we show that distinct sets of miRNA characterise each time point whilst CK fails to differentiate between them. MATERIALS AND METHODS Ethics Statement Wild-type and dy2J/dy2J (B6.WK-Lama2dy-2J/J) mice were purchased from Jackson laboratory and bred in the Biomedical Center according to institutional animal care guidel...
Source: PLOS Currents Muscular Dystrophy - August 27, 2018 Category: Neurology Authors: Bernardo Moreira Soares Oliveira Source Type: research

Health Care Transition Experiences of Males with Childhood-onset Duchenne and Becker Muscular Dystrophy: Findings from the Muscular Dystrophy Surveillance Tracking and Research Network (Md Starnet) Health Care Transitions and Other Life Experiences Survey
In this study only 1 in 4 males reported having a written summary to assist in the transition from a pediatric health care provider to an adult health care provider. Approximately 2 out of every 3 males aged 19-30 years reported ever changing a health care provider because their doctor only provided care for children, indicating that the majority of young men with DMD are making a health care transition to adult providers. The lack of written summary may be due to a lack of care coordination services. In this study, approximately 1 in 10 males had a primary care office and fewer than 1 in 3 males had a neuromuscular office...
Source: PLOS Currents Muscular Dystrophy - August 21, 2018 Category: Neurology Authors: Pangaja Paramsothy Source Type: research

A Pilot Survey Study of Adherence to Care Considerations for Duchenne Muscular Dystrophy
Conclusion This study showed adherence to many of the assessments and interventions suggested in the Care Considerations. The areas showing less consistency could be classified as derived from expert opinion with little supporting data. Improvement in the implementation of all aspects of recommended care requires continued study into the health impact of the proposed recommendations and continued advocacy for coverage by agencies. Corresponding Author Kristin Conway, PhD, Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, Iowa 52240, USA; Telephone: 319-335-4641 Email: kristin-casper...
Source: PLOS Currents Muscular Dystrophy - May 11, 2018 Category: Neurology Authors: kmcaspers Source Type: research

Greater Colo-Rectal Activation Phenotype in Exercised mdx Mice
INTRODUCTION Duchenne Muscular Dystrophy (DMD) is an X-­linked genetic disease characterized by the lack of the Dystrophin protein in the muscle tissue of affected individuals. While the predominant problem associated with DMD lies with the striated skeletal and cardiac muscles, a high percentage of DMD patients also suffer from gastrointestinal dysfunction. Constipation, gastric hypomotility, gastric dilation, and delayed gastric emptying are among the gastrointestinal motor abnormalities seen in DMD patients 1, 2, 3, 4. mdx mice, the animal model of DMD, also present symptoms of digestive dysfunction. Dystrophic mic...
Source: PLOS Currents Muscular Dystrophy - May 2, 2018 Category: Neurology Authors: mnearing Source Type: research

Are Soy Products Effective in DMD?
Discussion There were no significant differences in diet consumption or in mouse weight gain between the control and experimental diets over the course of the 12 weeks of treatment, nor were there any observable adverse effects on the mice. Comparison of wire hang times over the 12 weeks of treatment using the maximum holding impulse (weight x time)13 relative to the start of treatment (100%) as a measure revealed a slight decline in wire hang times in animals on the control diet (Figure 1). Isoflavones and isoflavones with BBI showed a slight and sustained increase in wire hang times over the course of the treatment, but ...
Source: PLOS Currents Muscular Dystrophy - March 27, 2018 Category: Neurology Authors: Steve J Winder Source Type: research

Are Soy Products Effective in DMD?
Discussion There were no significant differences in diet consumption or in mouse weight gain between the control and experimental diets over the course of the 12 weeks of treatment, nor were there any observable adverse effects on the mice. Comparison of wire hang times over the 12 weeks of treatment using the maximum holding impulse (weight x time) 13 relative to the start of treatment (100%) as a measure revealed a slight decline in wire hang times in animals on the control diet (Figure 1). Isoflavones and isoflavones with BBI showed a slight and sustained increase in wire hang times over the course of the treatment, but...
Source: PLOS Currents Muscular Dystrophy - March 27, 2018 Category: Neurology Authors: Gemma Marston Source Type: research

The Relationship Between Bone Mineral Density and Cardiovascular Function in Duchenne Muscular Dystrophy: A Retrospective Cohort Study
In this study, we explored the relationship between BMD and cardiovascular health, and observed no association between BMD and LVEF. The primary results were in the opposite direction than the hypothesized direction, with the model beta coefficient for BMD indicating a negative relationship with LVEF; however, the size of the effect BMD had on LVEF was very small and not statistically significant. The secondary linear regression analyses provided consistent results with the primary linear regression, indicating that the primary results are sensitive to a variety of slightly modified conditions. It is possible that the nul...
Source: PLOS Currents Muscular Dystrophy - March 22, 2018 Category: Neurology Authors: Tara Anne Kervin Source Type: research

Collective Statement Regarding Patient Access to Approved Therapies from the Center Directors of Parent Project Muscular Dystrophy ’s Certified Duchenne Care Centers
Conclusion Recent health insurance policies for DMD products have been constructed with limited input from neuromuscular specialists directly involved in patient care and without patient input. In order to ensure that policy determinations reflect best clinical practice, we implore insurers to work with neuromuscular specialists leading the PPMD Certified Duchenne Care Center teams, as well as patients and families, in developing policies. We represent a collective body of clinicians and clinical investigators, leading the world’s DMD care, registries, clinical trials, research, and natural history studies. We are co...
Source: PLOS Currents Muscular Dystrophy - March 15, 2018 Category: Neurology Authors: Cristian Ionita Source Type: research

A Review of Mathematical Models for Muscular Dystrophy: A Systems Biology Approach
Discussion With new developments in computational power and data availability, a growing amount of research is using a systems biology approach to understand pathogenesis and progression of disease. Effective and integrated in vitro and in silico models could inform biological phenomena, even without the need of a living subject. For instance, over the last few decades, collagen hydrogel with muscle derived cells (CHMDCs) have promised to revolutionize in vitro experiments and tissue engineering. For CHMDCs to reach the envisioned use, verification by use of mathematical simulations are needed. Recently while examining sha...
Source: PLOS Currents Muscular Dystrophy - February 16, 2018 Category: Neurology Authors: Matthew Houston Source Type: research

Epigenetic Regulators Modulate Muscle Damage in Duchenne Muscular Dystrophy Model
We report a follistatin-independent mechanism protecting against fibre damage. RESULTS To test whether Dystrophin absence affects HAT’s expression we performed quantitative real-time PCR (qPCR) for p300 and/or CBP (crebbp) transcripts (Figure 1A). Two-way ANOVA shows highly significant differences [F(1,24)=31.5, p
Source: PLOS Currents Muscular Dystrophy - December 21, 2017 Category: Neurology Authors: fbajanca Source Type: research

Influenza A Virus Infection Damages Zebrafish Skeletal Muscle and Exacerbates Disease in Zebrafish Modeling Duchenne Muscular Dystrophy
DISCUSSION Here, we investigated the effects of an infectious disease on skeletal muscle tissue alone and in combination with a genetic muscle disease. We found that human IAV can infect zebrafish muscle fibers and cause fiber damage via loss of sarcolemma integrity and/or loss of ECM adhesion external to the sarcolemma. Additionally, we showed that molecular and cellular markers of inflammation are present in muscle tissue in response to IAV infection. Finally, we showed that an infectious disease in combination with a genetic muscle disease greatly worsens the severity of muscle tissue degeneration. Taken together, our r...
Source: PLOS Currents Muscular Dystrophy - October 25, 2017 Category: Neurology Authors: Clarissa Henry Source Type: research

Benefits of Prenatal Taurine Supplementation in Preventing the Onset of Acute Damage in the Mdx Mouse
This study aims to investigate the efficacy of taurine at ameliorating dystrophic symptoms in the mdx mouse at two distinct pathological stages (28 and 70 d). Taurine was supplemented prenatally and throughout the life of animals to ensure the maximum effect of the amino acid. This study addresses the importance of age as a key consideration for pathological relevance when screening for therapeutic supplements, as well as when investigating biochemical and physiological properties of muscle from mdx mice. Our results show that at 28 d, during the onset of acute muscle damage, taurine was effective at increasing muscle stre...
Source: PLOS Currents Muscular Dystrophy - September 22, 2017 Category: Neurology Authors: Robyn Murphy Source Type: research

Benefits of Pre-natal Taurine Supplementation in Preventing the Onset of Acute Damage in the Mdx Mouse
This study aims to investigate the efficacy of taurine at ameliorating dystrophic symptoms in the mdx mouse at two distinct pathological stages (28 and 70 d). Taurine was supplemented prenatally and throughout the life of animals to ensure the maximum effect of the amino acid. This study addresses the importance of age as a key consideration for pathological relevance when screening for therapeutic supplements, as well as when investigating biochemical and physiological properties of muscle from mdx mice. Our results show that at 28 d, during the onset of acute muscle damage, taurine was effective at increasing muscle stre...
Source: PLOS Currents Muscular Dystrophy - September 22, 2017 Category: Neurology Authors: Robyn Murphy Source Type: research

Three Novel Immune-deficient Mouse Models of Muscular Dystrophy
This study provides three novel severely immune-deficient mouse muscular dystrophy models that will be useful in the development of successful gene and cell therapies. We also characterize the models to provide valuable baseline phenotypic information about them. Comparing the results between strains may elucidate further the phenotypic differences between these three forms of muscular dystrophy, although we note that since the strains are not fully inbred, differences in modifier genes may be present between them that could affect phenotype. Materials and Methods Ethics statement The Stanford Administrative Panel on ...
Source: PLOS Currents Muscular Dystrophy - September 1, 2017 Category: Neurology Authors: cpichav Source Type: research

Three Novel Immune-deficient Mouse Models of Muscular Dystrophy
This study provides three novel severely immune-deficient mouse muscular dystrophy models that will be useful in the development of successful gene and cell therapies. We also characterize the models to provide valuable baseline phenotypic information about them. Comparing the results between strains may elucidate further the phenotypic differences between these three forms of muscular dystrophy, although we note that since the strains are not fully inbred, differences in modifier genes may be present between them that could affect phenotype. Materials and Methods Ethics statement The Stanford Administrative Panel on ...
Source: PLOS Currents Muscular Dystrophy - September 1, 2017 Category: Neurology Authors: cpichav Source Type: research

[MD-17-0009] The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression
Introduction Duchenne Muscular Dystrophy (DMD) is the most common and severe muscle disease presenting in childhood. It is caused by mutations in the dystrophin gene, located on the X chromosome, which causes a complete absence of dystrophin protein in muscle. Becker Muscular Dystrophy (BMD) is caused by partial absence of dystrophin; this disease is less severe and less common. As an X-linked disease, both diseases almost always affect males, though some females may be affected as well. Duchenne and Becker have a prevalence of 1 in 5000 males, in about a 2:1 ratio.1,2 People with Duchenne Muscular Dystrophy have progress...
Source: PLOS Currents Muscular Dystrophy - June 27, 2017 Category: Neurology Authors: Kathi Kinnett Source Type: research

The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression
Introduction Duchenne Muscular Dystrophy (DMD) is the most common and severe muscle disease presenting in childhood. It is caused by mutations in the dystrophin gene, located on the X chromosome, which causes a complete absence of dystrophin protein in muscle. Becker Muscular Dystrophy (BMD) is caused by partial absence of dystrophin; this disease is less severe and less common. As an X-linked disease, both diseases almost always affect males, though some females may be affected as well. DMD and BMD have a prevalence of 1 in 5000 males, in about a 2:1 ratio.1,2 People with Duchenne Muscular Dystrophy have progressive musc...
Source: PLOS Currents Muscular Dystrophy - June 27, 2017 Category: Neurology Authors: Kathi Kinnett Source Type: research

Duchenne Regulatory Science Consortium Meeting on Disease Progression Modeling for Duchenne Muscular Dystrophy
Conclusions The group concluded that they were interested in pursuing such a modeling approach based on consideration of muscle fat fraction, timed function tests, muscle strength, as well as optimized scales of function in ambulant and non-ambulant patients, with additional consideration of time to event analyses of specific disease milestones. The variables that are finally included in the model will be dictated by the data – both what data is in the integrated dataset and what early stage analyses of that data tells us about what is most relevant to the final model. The context of use of the model would be to fore...
Source: PLOS Currents Muscular Dystrophy - January 12, 2017 Category: Neurology Authors: Jane Larkindale Source Type: research

New Recommendation on Biological Materials Could Hamper Muscular Dystrophy Research
Conclusions If Recommendation 12.1 is applied to children, it would unduly restrict rare disease research by preventing the use of children’s biomaterials in research involving adults, or on anyone without the same condition and thereby constrict children’s right to benefit from the solidaristic actions of others. It would make efforts to improve data and biomaterials sharing for rare diseases more complex, time consuming and less efficient. Platforms such as RD Connect and BBMRI-ERIC which were designed to contribute to the efficacy and excellent of European research by easing access to resources, could be ren...
Source: PLOS Currents Muscular Dystrophy - December 21, 2016 Category: Neurology Authors: Pauline McCormack Source Type: research

Can Quantitative Muscle Strength and Functional Motor Ability Differentiate the Influence of Age and Corticosteroids in Ambulatory Boys with Duchenne Muscular Dystrophy?
In this study dimension point score sums were used in the analysis. Timed Motor Tests Four timed motor tests (TMTs) were assessed in this study including; assuming standing from supine on the floor, assuming standing from sitting on a bench (hips and knees at 90 degrees), climbing four standard stairs with assist of a railing, and ten-meter run on a level surface. Subjects were instructed to complete all measures as quickly as possible and were timed in seconds. Analysis Two-way analysis of variance (ANOVA), with treatment group (corticosteroid/naïve) and age (4-7 years, ≥ 8 years), was used to dete...
Source: PLOS Currents Muscular Dystrophy - July 8, 2016 Category: Neurology Authors: cbuckon Source Type: research

Prednisone and Deflazacort in Duchenne Muscular Dystrophy: Do They Play a Different Role in Child Behavior and Perceived Quality of Life?
In this study, we only used the syndrome scales of the CBCL. Syndromes are sets of concurrent problems that tend to co-occur together. Syndrome scales include anxious/depressed, withdrawn/depressed, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior and aggressive behavior. Syndrome scales are categorized into internalizing and externalizing behaviors. Internalizing behaviors are problems that are primarily within the individual and include anxious/depressed, withdrawn/depressed and somatic complaints, while externalizing behaviors are problems that mainly involve conflict wit...
Source: PLOS Currents Muscular Dystrophy - June 17, 2016 Category: Neurology Authors: Susan Sienko Source Type: research

Investigating Synthetic Oligonucleotide Targeting of Mir31 in Duchenne Muscular Dystrophy
In this study we therefore determined to investigate whether blockade of miR31 could be employed synergistically with exon-skipping, using PMO oligonucleotide chemistries already approved for use in clinical trials. Using an animal model of DMD, the mdx mouse (which carries a premature stop codon in dystrophin exon 23), and a dystrophic mouse cell culture line carrying the mdx mutation (H2KSF127), we combined the well-established mdx-specific skipping oligo (M23D)28 with PMOs representing “sponge”, “protector” and “miR31-analogue” sequences (schematic: Fig 1 B-E, sequences and hybridizat...
Source: PLOS Currents Muscular Dystrophy - June 16, 2016 Category: Neurology Authors: John CW Hildyard Source Type: research

A Modified Wire Hanging Apparatus for Small Animal Muscle Function Testing
Discussion The wire hanging test is based on the natural instinct of a mouse to avoid falling. The time that a mouse can hang for is determined by a number of factors, including the physical properties of the muscles, the number of limbs used and the weight of the mouse, as well as age and sex. Muscle disease such as muscular dystrophy, reduces hang times providing a rationale for using the test to determine the potential benefits of interventions. Mouse age and sex can be controlled in the experimental design, and weight can be accounted for in various ways in calculating the result. However, whether a mouse uses two or f...
Source: PLOS Currents Muscular Dystrophy - May 2, 2016 Category: Neurology Authors: efhoffman Source Type: research

Increased taurine in pre-weaned juvenile mdx mice greatly reduces the acute onset of myofibre necrosis and dystropathology and prevents inflammation
Introduction Duchenne Muscular Dystrophy (DMD) is a lethal, X-chromosome linked muscle disease affecting about 1 in 3500-6000 boys worldwide (Reviewed in 1,2). DMD is caused by the loss of functional dystrophin protein in muscle that results in increased necrosis and inflammation after muscle contraction34,5,6. Repeated cycles of widespread myofibre necrosis and progressive failure of regeneration (with replacement of myofibres by fatty and fibrous connective tissue) lead to the loss of muscle mass and function in DMD boys, with premature death often due to respiratory or cardiac failure (Reviewed in 1,7). There is no cure...
Source: PLOS Currents Muscular Dystrophy - April 29, 2016 Category: Neurology Authors: jessicaterrill Source Type: research

Investigating Synthetic Oligonucleotide Targeting of Mir31 in Duchenne Muscular Dystrophy
In this study we therefore determined to investigate whether blockade of miR31 could be employed synergistically with exon-skipping, using PMO oligonucleotide chemistries already approved for use in clinical trials. Using an animal model of DMD, the mdx mouse (which carries a premature stop codon in dystrophin exon 23), and a dystrophic mouse cell culture line carrying the mdx mutation (H2KSF127), we combined the well-established mdx-specific skipping oligo (M23D)28 with PMOs representing “sponge”, “protector” and “miR31-analogue” sequences (schematic: Fig 1 B-E, sequences and hybridizat...
Source: PLOS Currents Muscular Dystrophy - March 8, 2016 Category: Neurology Authors: John CW Hildyard Source Type: research

Dysferlinopathy Fibroblasts Are Defective in Plasma Membrane Repair
In conclusion, fibroblasts from dysferlinopathy patients and SJL mice showed attenuated membrane repair, and could be a research tool to monitor the effects of drug candidate including proteasome inhibitors on mutant dysferlin. Competing Interests The authors have declared that no competing interests exist. Correspondence The corresponding author can be contacted at cmatsuda@ncnp.go.jp. (Source: PLOS Currents Muscular Dystrophy)
Source: PLOS Currents Muscular Dystrophy - October 29, 2015 Category: Neurology Authors: Chie Matsuda Source Type: research

Enhanced Reprogramming Efficiency and Kinetics of Induced Pluripotent Stem Cells Derived from Human Duchenne Muscular Dystrophy
In this study, we demonstrated an efficient generation of DMD-iPSCs on immortalized human feeders with improved reprogramming efficiency, and kinetics. Materials and Methods Derivation of DMD primary human fibroblast cells (hFib) Our study was conducted only after obtaining written informed consent from the parents or guardians of the participants and approval from the Institutional Committee for Stem Cell Research and Therapy Institutional (Ref 23/02/10-A5) and the Institute Ethics Committee All India Institute of Medical Science (Ref. IEC/NP-82/2010). Skin biopsies were taken from DMD patients ages 6-12 years old...
Source: PLOS Currents Muscular Dystrophy - September 3, 2015 Category: Neurology Authors: Pooja Teotia Source Type: research

Imperatives for DUCHENNE MD: a Simplified Guide to Comprehensive Care for Duchenne Muscular Dystrophy
Introduction The muscular dystrophies (MD) are a group of genetically heterogeneous muscle diseases marked by progressive wasting and weakness of the skeletal and cardiac muscles1. Duchenne muscular dystrophy (DMD) is the most common and most severe form. It is an X-linked disorder affecting 1 in 5000 live male births2,3. DMD is caused by mutations in the DMD gene, which encodes the muscle fiber membrane protein dystrophin. Deficiency or complete absence of dystrophin makes muscle fibers sensitive to damage upon contraction, leading to plasma membrane leakage and muscle fiber degeneration, which eventually leads to progres...
Source: PLOS Currents Muscular Dystrophy - August 7, 2015 Category: Neurology Authors: Kathi Kinnett Source Type: research

Correction: A Randomized, Double-Blind Trial of Lisinopril and Losartan for the Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy
Correction The fourth author was inadvertently left off the original author listing. Laurence Viollet-Callendret has been added to the original article as the fourth author. Reference Allen HD, Flanigan KM, Thrush PT, Viollet-Callendret L, Dvorchik I, Yin H, Canter C, Connolly AM, Parrish M, McDonald CM, Braunlin E, Colan SD, Day J, Darras B, Mendell JR. A Randomized, Double-Blind Trial of Lisinopril and Losartan for the Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy. PLOS Currents Muscular Dystrophy. 2013 Dec 12. Edition 1. doi: 10.1371/currents.md.2cc69a1dae4be7dfe2bcb420024ea865. View Article (Source: PLOS...
Source: PLOS Currents Muscular Dystrophy - March 6, 2015 Category: Neurology Authors: ploscurrents Source Type: research

The FVB Background Does Not Dramatically Alter the Dystrophic Phenotype of Mdx Mice
Introduction Duchenne muscular dystrophy (DMD) is an X-linked lethal progressive muscle wasting disorder mainly affecting boys. It is caused by mutations in the dystrophin gene, one of the largest and most conserved genes in the genome (reviewed in 1 ). Numerous mouse models have been used to study dystrophin function and DMD pathogenesis (reviewed in 2-5). Among these, the mdx mouse is the most frequently used model (reviewed in 6). First described in 1984 by Bulfield and colleagues as a spontaneous myopathy model in C57/BL10 (BL10) mice, mdx mice carry a nonsense mutation in the exon 23 of the dystrophin gene 7,8. Transg...
Source: PLOS Currents Muscular Dystrophy - February 10, 2015 Category: Neurology Authors: Nalinda B. Wasala Source Type: research

Online Self-Report Data for Duchenne Muscular Dystrophy Confirms Natural History and Can Be Used to Assess for Therapeutic Benefits
INTRODUCTION The study of rare diseases by traditional methods, such as clinical trials or natural history studies, is limited by the challenges and costs of recruiting an adequate sample. Self-report registry-based approaches have important potential advantages including the ability to cost-effectively grow the study sample, but at the risk of potential reductions in data quality1. One disease for which patient registries have the potential to impact our understanding of treatment is Duchenne muscular dystrophy (DMD; OMIM #310200). DMD is the most common form of progressive childhood-onset muscular dystrophy, affecting 1....
Source: PLOS Currents Muscular Dystrophy - October 17, 2014 Category: Neurology Authors: richardwang Source Type: research

The 6 Minute Walk Test and Performance of Upper Limb in Ambulant Duchenne Muscular Dystrophy Boys
Discussion The results of this study confirm that involvement of upper limb function can already be found in ambulant DMD boys11 . Not surprisingly the first signs of involvement are related to the shoulder domain with a % of patients not able to perform antigravity shoulder abduction and flexion movements, such as bringing the hand or progressive weights at shoulder or eye level by the side or in front. Because of the proximal to distal gradient of progression of upper limb involvement we observed less changes in the elbow or distal domain that are classically more involved after boys lose ambulation. When we correlated t...
Source: PLOS Currents Muscular Dystrophy - October 7, 2014 Category: Neurology Authors: eugeniomercuri Source Type: research

Non-Radioactive Detection of Trinucleotide Repeat Size Variability
Introduction The expansion of trinucleotide repeat sequences (TNRs) was identified as the causative mutation in more than 20 neurological and neuromuscular disorders, such as Huntington’s disease (HD), myotonic dystrophy type 1 (DM1), fragile X syndrome (FRAXA) and Friedreich’s ataxia (FRDA) 1. Non-affected individuals usually carry
Source: PLOS Currents Muscular Dystrophy - March 6, 2014 Category: Neurology Authors: Stéphanie Tomé Source Type: research

Identification and Validation of Quantitative PCR Reference Genes Suitable for Normalizing Expression in Normal and Dystrophic Cell Culture Models of Myogenesis
We examined gene expression of a comparatively large set of putative reference genes throughout myogenic differentiation in two healthy and one disease-model murine cell culture systems: the commonly-used C2C12 myoblast line15 , and the immortomouse-derived myoblast lines H2K2B416 and H2KSF117 . The latter cell line (SF1) carries the mdx mutation (a premature termination codon in exon 23 of the dystrophin gene) and is thus a cell line model for dystrophic muscle. We here present data suggesting a common set of candidates for normalizing gene expression during myogenesis in these three culture models of murine muscle differ...
Source: PLOS Currents Muscular Dystrophy - March 6, 2014 Category: Neurology Authors: jhildyard Source Type: research

Validity, Reliability, and Sensitivity of a 3D Vision Sensor-based Upper Extremity Reachable Workspace Evaluation in Neuromuscular Diseases
This study assesses the validity, reliability, sensitivity, and utility of a newly developed stereo camera-based system to assess upper extremity 3D reachable workspace envelope surface area and relative surface area. We assessed the validity by determining whether subjects with documented impairment in ROM as measured by the Brooke scale (Table 2) would exhibit significantly reduced reachable surface areas than controls, by quadrant and total area. To assess the reliability of the system, three repeated trials were performed on the same day for the dominant and the non-dominant arm. A one-way repeated measures analysis of...
Source: PLOS Currents Muscular Dystrophy - December 12, 2013 Category: Neurology Authors: Jay J. Han Source Type: research

A Randomized, Double-Blind Trial of Lisinopril and Losartan for the Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy
In conclusion, there is no difference between the effects of lisinopril versus losartan on EF improvement in DMD boys with CM. The drugs were safe. Thus, this study opens the opportunity to study muscle function in younger boys with DMD to see if the skeletal muscle improvement seen in the mdx mouse following treatment with an ARB might also be demonstrated in DMD boys. 17 Competing Interests The authors have declared that no competing interests exist. Correspondence Hugh D. Allen MD, Heart Center, Texas Children’s Hospital, 6621 Fannin St. Suite 19469, Houston, TX, 77030 E-mail: hdallen@texaschildrens.org Auth...
Source: PLOS Currents Muscular Dystrophy - December 12, 2013 Category: Neurology Authors: Hugh D. Allen Source Type: research

Autophagy is Impaired in the Tibialis Anterior of Dystrophin Null Mice
Background Duchenne Muscular Dystrophy (DMD) is the most common neuromuscular disorder. DMD is caused by the complete absence of the dystrophin protein, which leads to extensive muscle degeneration and regeneration followed by substitution of muscle with fibrotic and adipose tissues 1,2. No cure is yet available, but several therapeutic approaches aiming at reversal of the ongoing degeneration have been investigated in preclinical and clinical settings with disappointing results 3,4,5. Currently, drugs intended to induce skeletal muscle hypertrophy via Akt-mediated protein synthesis are in preclinical (e.g. valproic acid) ...
Source: PLOS Currents Muscular Dystrophy - November 22, 2013 Category: Neurology Authors: pietrospitali Source Type: research

Absence of a Major Role for the Snai1 and Snai3 Genes in Regulating Skeletal Muscle Regeneration in Mice
Discussion Our results demonstrate effective skeletal muscle regeneration after cardiotoxin-mediated injury in Snai3 homozygous mutant (Snai3null/Snai3null or Snai3-EYFP/Snai3-EYFP) mice. We further show that mice with skeletal muscle-specific deletion of the Snai1 gene on a Snai3 null genetic background exhibit the same general level of skeletal muscle regeneration as the Snai3 mutant homozygotes. While our histopathological analyses cannot exclude minor regeneration defects in the Snai3 single or Snai1/Snai3 double mutants, it is clear that substantial muscle regeneration occurs after cardiotoxin-mediated injury in these...
Source: PLOS Currents Muscular Dystrophy - November 8, 2013 Category: Neurology Authors: nortoc1 Source Type: research

Effects of Dantrolene Therapy on Disease Phenotype in Dystrophin Deficient mdx Mice
In this study we demonstrated that Dantrolene treatment has no significant beneficial effects at the tested dose in young mdx mice. Dantrolene failed to improve the muscle phenotype as measured by functional, behavioral, histological, and imaging assays. The exception being CK levels, which were significantly decreased by Dantrolene treatment. Dantrolene is a known muscle relaxant and used for the treatment of malignant hyperthermia 11. It decreases the calcium released in skeletal muscle upon stimulation, resulting in decreased muscle contraction 19. In fact, functional assessments such as grip strength and open field act...
Source: PLOS Currents Muscular Dystrophy - November 8, 2013 Category: Neurology Authors: James Quinn Source Type: research

The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy
Introduction Muscular dystrophies are genetic disorders characterized by progressive muscle degeneration and impaired muscle function. Many muscular dystrophies are caused by mutations in genes that encode components of the Dystrophin-glycoprotein complex 1,2, including Duchenne muscular dystrophy (DMD), which is caused by mutations in the Dystrophin (DMD) gene 3. Mechanisms that contribute to muscle degeneration in the muscular dystrophies include muscle membrane instability, disrupted calcium homeostasis, and oxidative stress 2. Gene-mediated and cell-mediated therapeutic strategies for DMD hold tremendous promise, but t...
Source: PLOS Currents Muscular Dystrophy - September 17, 2013 Category: Neurology Authors: njohnso8 Source Type: research

PLOS Currents no longer accepts new submissions.
After much consideration and a full review of the platform, we have made the difficult decision to cease publication of PLOS Currents. We no longer accept new submissions to the journal. Authors of articles under review at PLOS Currents have been contacted by the journal office. All PLOS Currents content remains available here and in PubMedCentral, and is indexed in PubMed. All enquiries can be addressed to currents@plos.org (Source: PLOS Currents Muscular Dystrophy)
Source: PLOS Currents Muscular Dystrophy - March 22, 2013 Category: Neurology Authors: Liz Flavall Tags: carousel Source Type: research